Adenoviral transduction of human ‘clinical grade’ immature dendritic cells enhances costimulatory molecule expression and T-cell stimulatory capacity

Rouard, Hélène; Léon, Anne; Klonjkowski, Bernard; Marquet, J; Tennezé, Laurent; Plonquet, Anne; Agrawal, Samir; Abastado, Jean-Pierre; Éloit, Marc; Farcet, Jean‐Pierre; Delfau‐Larue, Marie‐Hélène

doi:10.1016/s0022-1759(00)00214-3

Cited by 58 publications

(43 citation statements)

References 30 publications

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“…Dendritic cells are potent antigen presenting cells and, therefore, are the target of vaccine strategies (Rea et al, 1999;Rouard et al, 2000;Wan et al, 1997). A complete understanding of the mechanism and consequences of Ad species B infection of these cells may facilitate development of vectors that will stimulate an effective immune response.…”

Section: Discussionmentioning

confidence: 99%

Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors

et al. 2006

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Alternate serotypes of adenovirus (Ad), including Ads of species B, are being explored to circumvent the disadvantages of Ad serotype 5 gene delivery vectors. Whereas the majority of human Ads utilize the Coxsackievirus and adenovirus receptor (CAR), none of the Ad species B use CAR. Ad species B is further divided into two subspecies, B1 and B2, and utilizes at least two classes of receptors: common Ad species B receptors and B2 specific receptors. CD46 has been implicated as a B2-specific receptor. Ad serotype 3 (Ad3), a member of B1, utilizes CD80 and CD86 as cellular attachment receptors. The receptor-interacting Ad fiber-knob domain is highly homologous among species B Ads. We hypothesized that other members of Ad species B may utilize CD80 and CD86 as cellular attachment receptors. All tested species B members showed specific binding to cells expressing CD80 and CD86, and the Ad fiber-knob domain from both B1 and B2 Ad efficiently blocked CD80-and CD86-mediated infection of Ad3 vectors. Members of both B1 and B2 demonstrated CD80-and CD86-specific infection of CHO cells expressing CD80 and CD86. Therefore, all of the members of Ad species B utilize CD80 and CD86 for infection of cells.

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Section: Discussionmentioning

confidence: 99%

Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors

et al. 2006

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“…This conjecture is supported by several reports that demonstrated the promotion of DC maturation by Ad infection. [51][52][53] In particular, Morelli et al 54 reported that Ad-infected DCs matured via a NFkB-dependent pathway, regardless of transgenic sequences or Ad-genome transcription. However, Dietz et al 55 demonstrated that the expression of CD83 and IL-12 p40 was unaffected by Ad infection or transferred gene expression.…”

Section: Discussionmentioning

confidence: 99%

Gene transduction efficiency and maturation status in mouse bone marrow-derived dendritic cells infected with conventional or RGD fiber-mutant adenovirus vectors

et al. 2003

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Since dendritic cells (DCs) play a critical role in establishing antigen-specific adaptive immune responses, in the past several years, therapeutic strategies using genetically modified DCs against cancer and infectious diseases have attracted increasing attention. In the present study, we demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) exhibited markedly superior gene transduction efficiency in mouse bone marrow-derived DCs (mBM-DCs) compared to conventional adenovirus vector (Ad). Likewise, this vector exhibited superior major histocompatibility complex class I-restricted presentation of antigen derived from the delivered gene in mBM-DCs. In order to investigate the effect of Ad-infection on the DC-differentiation process (maturation), we used three types of AdRGD and three conventional Ad to transduce mBM-DCs. These vectors carried either no transgene, LacZ gene, or gp100 gene. Infection by any of the Ad vectors enhanced the expression of MHC class II molecules in mBM-DCs. CD80, CD86, and CD40 expression and IL-12 production were more efficient in AdRGD-infected mBM-DCs than in conventional Adinfected cells. Contrary to our expectations, endocytotic activity of mBM-DCs decreased only slightly upon Ad-infection, whereas antigen uptake by lipopolysaccharide (LPS)-driven mature mBM-DCs was significantly impaired. However, our reverse transcription-polymerase chain reaction analysis revealed that Ad-infection resulted in the upregulation of the chemokine receptor CCR7 and downregulation of CCR6 in mBM-DCs and LPS-stimulated cells. We, therefore, concluded that Ad-infection directly influenced DC-maturation, although the effects were milder than under LPS-stimulation. In addition, this change in the immunologic properties of DCs resulted primarily from an increase in the number of Ad-particles capable of invading the cells rather than from the expression of foreign genes. AdRGD-infection caused greater induction of maturation than conventional Adinfection, irrespective of the type of transgene inserted.

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“…The stimulation of intracellular signaling pathways seems to be required for the early phases of the viral cycle since activated cAMP-dependent protein kinase and p38/MAPK boost microtubule-mediated nuclear addressing of the virus (13). Ad has been found to modulate dendritic cell (DC) maturation by increasing the expression of major histocompatibility complex and costimulatory molecules and, at least for murine DC, by inducing the secretion of IL12 (15)(16)(17)(18). We and others have shown that such activated DC are fully competent for initiating protective immune responses (19 -21).…”

Section: T Cell Response In Vivomentioning

confidence: 99%

The Maturation of Murine Dendritic Cells Induced by Human Adenovirus Is Mediated by the Fiber Knob Domain

Molinier‐Frenkel

Prévost-Blondel

Hong

et al. 2003

Journal of Biological Chemistry

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We investigated the mechanism of adenovirus serotype 5 (Ad5)-mediated maturation of bone marrow-derived murine dendritic cells (DC) using (i) Ad5 vectors with wildtype capsid (AdE1°, AdGFP); (ii) Ad5 vector mutant deleted of the fiber C-terminal knob domain (AdGFP⌬knob); and (iii) capsid components isolated from Ad5-infected cells or expressed as recombinant proteins, hexon, penton, penton base, full-length fiber, fiber knob, and fiber mutants. We found that penton capsomer (penton base linked to its fiber projection), full-length fiber protein, and its isolated knob domain were all capable of inducing DC maturation, whereas no significant DC maturation was observed for hexon or penton base alone. This capacity was severely reduced for AdGFP⌬knob and for fiber protein deletion mutants lacking the ␤-stranded region F of the knob (residues Leu-485-Thr-486). The DC maturation effect was fully retained in a recombinant fiber protein deleted of the HI loop (Fi⌬HI), a fiber (Fi) deletion mutant that failed to trimerize, suggesting that the fiber knob-mediated DC activation did not depend on the integrity of the HI loop and on the trimeric status of the fiber. Interestingly, peptide-pulsed DC that had been stimulated with Ad5 knob protein induced a potent CD8 ؉

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Adenoviral transduction of human ‘clinical grade’ immature dendritic cells enhances costimulatory molecule expression and T-cell stimulatory capacity

Cited by 58 publications

References 30 publications

Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors

Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors

Gene transduction efficiency and maturation status in mouse bone marrow-derived dendritic cells infected with conventional or RGD fiber-mutant adenovirus vectors

The Maturation of Murine Dendritic Cells Induced by Human Adenovirus Is Mediated by the Fiber Knob Domain

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